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Objective: To explore the antileishmanial effect of tioxolone and its niosomal form against Leishmania tropica. Methods: Tioxolone niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. The cytotoxicity of tioxolone and its niosomal form was measured by MTT assay, leishmanicidal activity against promastigote and amastigote by MTT assay, apoptosis by flow cytometry, IL-12, IL-10 and metacaspase gene expression levels by q-PCR. Results: Span/Tween 40 and Span/Tween 60 niosomes had good physical stability as depicted in their size distribution curves and high encapsulation efficiency (>99%). The release profile of the entrapped compounds showed Fickian's model of tioxolone delivery based on diffusion through lipid bilayers. With the IC
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In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 μg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.
Subject(s)
Apoptosis , Gene Expression , In Vitro Techniques , Interleukin-10 , Interleukin-12 , Leishmania tropica , Leishmania , Leishmaniasis, Cutaneous , Liposomes , Methods , Up-RegulationABSTRACT
Objective: To explore the antileishmanial effect of tioxolone and its niosomal form against Leishmania tropica. Methods: Tioxolone niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. The cytotoxicity of tioxolone and its niosomal form was measured by MTT assay, leishmanicidal activity against promastigote and amastigote by MTT assay, apoptosis by flow cytometry, IL-12, IL-10 and metacaspase gene expression levels by q-PCR. Results: Span/Tween 40 and Span/Tween 60 niosomes had good physical stability as depicted in their size distribution curves and high encapsulation efficiency (>99%). The release profile of the entrapped compounds showed Fickian's model of tioxolone delivery based on diffusion through lipid bilayers. With the IC50 value for amastigote as (24.5±2.1) μg/mL and selectivity index as 10.5, the Span/Tween 60 niosome (NT2) had a superior effect to other drugs. The CC50 value and IC50 of promastigote value for NT2 were (257.5±24.5) μg/mL and (164.8±20.6) μg/ mL, respectively. The flow cytometric analysis showed that tioxolone and niosomal forms induced apoptosis of Leishmania tropica promastigotes in a dose-dependent manner. NT2 increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene. Conclusions: Niosomes of tioxolone play an immunomodulatory role in increasing Th1 cytokine profile and inhibiting the Th2 cytokine profile. It could be used for treatment of anthroponotic cutaneous leishmaniasis.
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OBJECTIVE:To study distribution and targeting of Gardenia jasminoides extract niosomes in rats. METHODS:G. jasminoides extract niosomes were prepared by modified thin film dispersion method. 30 rats were randomly divided into G. jasmin-oides extract group(57 mg/kg)and G. jasminoides extract liposome group(131 mg/kg)according to their weight. They were given relevant medicine intragastrically,once a day,for consecutive 7 days. 1 h after last administration,heart,liver,spleen,lung and kidney tissue were isolated,and HPLC method was adopted to the contents of active ingredients gardenoside in them. The targeting of G. jasminoides extract niosomes was evaluated by DTI quantitatively. RESULTS:Compared with G. jasminoides extract group, the contents of gardenoside in heart,spleen and brain tissue of rats increased significantly in G. jasminoides extract niosomes group (P<0.01),and DTI were 1.718,1.972 and 13.071;the contents of gardenoside in liver and kidney decreased significantly (P<0.01),and DTI were 0.431 and 0.467,respectively. CONCLUSIONS:G. jasminoides extract niosomes change the distribution of gardenoside in rats,showing brain targeting effect and decreasing first pass effect for liver.
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OBJECTIVE: To prepare nonionic surfactant niosomes by multiple emulsion freeze-drying method and study their encapsulation effects for the water-soluble drug, methotrexate.
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Natural maltodextrin, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, maltodextrin seem to be the most promising materials in the preparation of niosome carriers. This study aimed to optimize and characterize the formulation of natural maltodextrin-based niosome. The natural maltodextrin was made from cilembu sweet potato starch which used partial starch hydrolysis method by α-amylase enzyme. Proniosome and niosome formulations used three various concentration of surfactant (sorbitan monostearat) which about 5 mmol, 7.5 mmol, and 10 mmol for formula 1 (F1), formula 2 (F2), and Formula 3 (F3) respectively. In addition, physical and chemical characterizations had been done to characterize maltodextrin, proniosome, and niosome. The Dextrose Equivalent (DE) value of natural maltodextrin was 7.99+0.11. Furthermore, the vesicle size of proniosome was in the range of 5μ to 13μ. The entrapment percentages of piroxicam in niosome formulations were 72.5+1.1%,, 76+1.7 %, and 77.5+1.9 % for FI, F2 and F3 respectively. It can be concluded that the result provided an indication of natural maltodextrin from Cilembu sweet potato starch are potentialy carrier in the proniosome preparation which can be used for producing niosomes.
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OBJECTIVE: To study the influences of Gemini surfactant and sodium chloride (NaCl) on the physicochemical properties and encapsulation efficiency of ofloxacin niosomes for developing new drug delivery system. METHODS: The non-ionic surfactant noisome was prepared by thin film hydration-ultrasonic method, taking non-ionic Gemini surfactant, Span80 and cholesterol as capsule wall materials and ofloxacin as model drug. And the influences of factors such as the amount of surfactant, salt and hydration volume etc on the vesicle size, Zeta potential, encapsulation efficiency, stability and in vitro release behaviors of the ofloxacin niosomes were studied and the optimal prescription was obtained. RESULTS: The encapsulation efficiency and the particle size distribution of the niosomes were significantly improved by Gemini surfactant. And the best ratio of the capsule wall materials was as follows: Span80-CHOL-Gemini=1:1:1. The influences of NaCl on the properties of the noisomes were as follows; the amount of drug loading was improved significantly and the absolute value of the Zeta potential decreased obviously with NaCl being added in the aqueous phase. The optimal NaCl concentration was 10 mg · mL-1. The in vitro release test showed that only 62.8% ofloxacin was released from the niosomes in 7 h in artificial gastric juice and artificial intestinal fluid, suggesting a good sustained release trend. CONCLUSION: Gemini surfactant niosomes show significant salt tolerance and obviously decrease the release rate of ofloxacin. The non-ionic Gemini surfactant may be used as a capsule wall material for new drug release system.